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Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2008 May 15; Vol. 14 (10), pp. 3185-92. - Publication Year :
- 2008
-
Abstract
- Purpose: Because the combination of multiple modalities for cancer treatment is more likely to generate more potent therapeutic effects for the control of cancer, we have explored the combination of chemotherapy using cisplatin, which is routinely used in chemotherapy for advanced cervical cancer, with immunotherapy using DNA vaccines encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 antigen (CRT/E7) in a preclinical model.<br />Experimental Design: We characterized the combination of cisplatin with CRT/E7 DNA vaccine using different regimen for its potential ability to generate E7-specific CD8+ T-cell immune responses as well as antitumor effects against E7-expressing tumors.<br />Results: Our results indicate that treatment of tumor-bearing mice with chemoimmunotherapy combining cisplatin followed by CRT/E7 DNA generated the highest E7-specific CD8+ T-cell immune response and produced the greatest antitumor effects and long-term survival as well as significant levels of E7-specific tumor-infiltrating lymphocytes compared with all the other treatment regimens. Furthermore, we found that treatment with cisplatin leads to the cell-mediated lysis of E7-expressing tumor cells in vitro and increased number of E7-specific CD8+ T-cell precursors in tumor-bearing mice. In addition, we observed that E7-specific CD8+ T cells migrate to and proliferate in the location of TC-1 tumors in mice treated with cisplatin.<br />Conclusions: Thus, our data suggest that chemoimmunotherapy using cisplatin followed by CRT/E7 DNA vaccine is an effective treatment against E7-expressing tumors and may potentially be translated into the clinical arena.
- Subjects :
- Animals
Biolistics
Calreticulin genetics
Cancer Vaccines administration & dosage
Cancer Vaccines immunology
Combined Modality Therapy
Cytotoxicity, Immunologic
Female
Flow Cytometry
Histocompatibility Antigens Class I biosynthesis
Lymphocytes, Tumor-Infiltrating immunology
Mice
Neoplasms, Experimental immunology
Oncogene Proteins, Viral genetics
Papillomavirus E7 Proteins
Polymerase Chain Reaction
Vaccines, DNA administration & dosage
Vaccines, DNA immunology
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines therapeutic use
Cisplatin therapeutic use
Neoplasms, Experimental therapy
Oncogene Proteins, Viral immunology
Vaccines, DNA therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 14
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 18483387
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-08-0037